The background here is that ED drugs work by inhibiting phosphodiesterase-5, and the down-regulation of that enzyme also occurs in some biochemical pathways that lead to melanoma, so we can put a check mark next to biologic plausibility. Human evidence of the link, prior to this week, involves a cohort study in the US which suggested that men taking sildenafil had a nearly two-fold increase in melanoma risk (but of the melanoma cases, only 14 had been taking sildenafil).

The researchers used a preexisting cohort of around 600,000 Swedish men. In that group, there were roughly 4000 cases of melanoma, which they matched (based on year of birth) to 20,000 controls.

In unadjusted analyses, the PDE-5 inhibitors were associated with about a 30% increase in melanoma. This persisted after adjusting for a smattering of confounders such as income and comorbidity scores, but the authors state that they believed their adjustments were incomplete. If the association were causal, it would mean an additional 7 cases of melanoma out of every 100,000 men taking ED drugs.

But despite the association, two major findings make the link hard to believe. First, the relationship between ED drugs and melanoma was only seen in those who had a one-time prescription for the drug. If the drugs were causal, wed expect an increase in risk among those who got more prescriptions. In addition, the researchers found a link between ED drug use and basal-cell carcinoma, a malignancy that doesnt have a known PDE5 link. This all suggests that men who take ED drugs might also engage in other behaviors that increase the risk of melanoma - like taking vacations in sunny places.

Just to make it clear that were not totally out of the woods here, I should note that this PDE5 pathway only appears to be relevant in the roughly 50% of melanoma cases that have a BRAF mutation - its conceivable that if the researchers could stratify by BRAF status, they may have found a link. For now, though, we can rest easy - data linking ED drugs and melanoma is simply not that firm.